COL11A1

The COL11A1 gene provides instructions for making one component of type XI collagen, called the pro-alpha1(XI) chain. Type XI collagen adds structure and strength to the connective tissues that support the body's muscles, joints, organs, and skin. Type XI collagen is normally found in cartilage, a tough but flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Type XI collagen is also part of the clear gel that fills the eyeball (the vitreous), the inner ear, and the center portion of the discs between the vertebrae in the spine (nucleus pulposus).

The pro-alpha1(XI) chain combines with two other collagen chains (pro-alpha2(XI) and pro-alpha1(II)) to form a procollagen molecule. These triple-stranded, ropelike procollagen molecules are then processed by enzymes in the cell. Once processed, procollagen molecules leave the cell and arrange themselves into long, thin fibrils that link to one another (cross-link) in the spaces around cells. The cross-linkages result in the formation of very strong mature type XI collagen fibers.

Type XI collagen also helps maintain the spacing and diameter of type II collagen fibrils. Type II collagen is an important component of the eye and mature cartilage tissue. The size and arrangement of type II collagen fibrils is essential for the normal structure of these tissues.

Stickler syndrome - caused by mutations in the COL11A1 gene

Mutations in the COL11A1 gene have been identified in some people with Stickler syndrome. Some mutations change one of the protein building blocks (amino acids) used to make the pro-alpha1(XI) chain. Other mutations cause segments of DNA to be skipped when the protein is being made, resulting in an abnormally short pro-alpha1(XI) chain. These alterations of type XI collagen impair its function, which can lead hearing loss, a tearing of the lining of the eye (retinal detachment), and abnormalities of the bones and joints.

Mutations in the COL11A1 gene are also responsible for some cases of Marshall syndrome, a disorder that is very similar to Stickler syndrome. In most mutations that cause this syndrome, a segment of DNA is skipped when the protein is made, resulting in an abnormally small pro-alpha1(XI) chain. This shortened protein hinders the formation of mature type XI collagen, which results in the features of Marshall syndrome. Whether Marshall syndrome represents a variant form of Stickler syndrome or a separate disorder is controversial.

other disorders - increased risk from variations of the COL11A1 gene

In some people, variations in the COL11A1 gene may increase the risk of developing osteoarthritis, a degenerative disease of joint cartilage. As a result of these genetic changes, incorrect amino acids are used in making the pro-alpha1(XI) chain of type XI collagen. The altered pro-alpha1(XI) chain may weaken collagen fibers, which could play a role in the erosion of cartilage in the joints, a characteristic feature of osteoarthritis.